E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Delirium state in critical ill patients |
Trattamento del delirium in pazienti adulti critici in terapia intensiva |
|
E.1.1.1 | Medical condition in easily understood language |
Delirium treatment in patients admitted to the Intensive Care Unit |
Trattamento del delirio in pazienti difficili in terapia intensiva |
|
E.1.1.2 | Therapeutic area | Diseases [C] - Nervous System Diseases [C10] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 21.0 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10071313 |
E.1.2 | Term | Hypoactive delirium |
E.1.2 | System Organ Class | 100000004873 |
|
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 21.0 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10012226 |
E.1.2 | Term | Delirium, cause unknown |
E.1.2 | System Organ Class | 100000004873 |
|
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 21.0 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10012220 |
E.1.2 | Term | Delirium due to a general medical condition |
E.1.2 | System Organ Class | 100000004873 |
|
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 21.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10042275 |
E.1.2 | Term | Subacute delirium |
E.1.2 | System Organ Class | 100000004873 |
|
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 21.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10013758 |
E.1.2 | Term | Drug-induced delirium |
E.1.2 | System Organ Class | 100000004873 |
|
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 21.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10000702 |
E.1.2 | Term | Acute delirium |
E.1.2 | System Organ Class | 100000004873 |
|
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 21.0 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10071314 |
E.1.2 | Term | Hyperactive delirium |
E.1.2 | System Organ Class | 100000004873 |
|
E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
To assess benefits and harms of haloperidol in adult, critically ill patients with delirium in the ICU. The primary objective is to determine, if haloperidol treatment in ICU patients with delirium will increase the number of days alive out of the hospital within 90 days. This primary objective includes 90 days mortality and length of hospital stay within 90 days after randomisation. |
Per valutare i benefici e i rischi del trattamento con aloperidolo in pazienti critici adulti con delirio in terapia intensiva. L'obiettivo primario è determinare se l'aloperidolo in pazienti con delirio in terapia intensiva aumenta il numero di giorni in vita senza ospedalizzazione entro 90 giorni. L'obiettivo primario include la mortalità a 90 giorni e la durata dell'ospedalizzazione entro 90 giorni dalla randomizzazione |
|
E.2.2 | Secondary objectives of the trial |
To investigate if haloperidol as compared with placebo in ICU patients with delirium will change the: - Number of days alive without delirium or coma in the ICU - Number of patients with one or more adverse reactions and/or the total number of adverse reactions to haloperidol compared with placebo. - Number of patients needing one or more doses of escape medicine and or the dosages of escape medicine per patient in the haloperidol Group compared with the placebo group - Number of days alive without mechanical ventilation in the 90-day trial period - One-year mortality after inclusion - Measurement of cognitive function one year after inclusion on selected trial sites. - A health economic analysis will be performed. |
Per studiare se l’aloperidolo confrontato con placebo in terapia intensiva nei pazienti con delirio modifica: -il numero di giorni in vita senza delirio o coma in ICU -il numero di pazienti con 1 o più reazioni avverse e/o numero totale di reazioni avverse all’aloperidolo rispetto al placebo -numero di pazienti che necessitano una o più terapie di “escape” e dosaggio per pazienti nel gruppo con aloperidolo rispetto al placebo -numero di giorni in vita senza ventilazione meccanica nei 90 giorni dello studio -mortalità ad 1 anno dopo inclusione -misurazione delle funzioni cognitive un anno dopo l’inclusione nei siti selezionati dello studio -analisi economica |
|
E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
- Acute admission to the ICU AND - Age ≥ 18 years AND - Diagnosed delirium with a validated screening tool as either CAM-ICU or ICDSC |
- ammissione acuta in terapia intensiva - età ≥ 18 anni - diagnosi di delirio effettuata con strumenti validati come CAM-ICU o ICDSC |
|
E.4 | Principal exclusion criteria |
- Contraindications to haloperidol - Habitual treatment with any antipsychotic medication - Permanently incompetent (e.g. dementia, mental retardation) - Delirium assessment non-applicable (coma or language barriers) - Withdrawal from active therapy or brain death - Fertile women (women < 50 years) with positive urine human chorionic gonadotropin (hCG) or plasma-hCG - Consent according to national regulations not obtainable - Patients under coercive measures by regulatory authorities - Patients with alcohol-induced delirium (delirium tremens) |
Controindicazioni all’aloperidolo Trattamento abituale con antipsicotici Permanentemente incompetente (demenza, ritardo mentale) Valutazione di delirio non praticabile (coma o barriere linguistiche) Sospensione delle cure attive o morte cerebrale Donne in età fertile con test delle urine positivo per la gonadotropina corionica Consenso non ottenibile Paziente sotto misure coercitive secondo l’autorità regolatoria Pazienti con delirio indotto da alcol (delirium tremens) |
|
E.5 End points |
E.5.1 | Primary end point(s) |
Days alive out of the hospital within 90 days post-randomisation |
Giorni in vita senza ospedalizzazione entro 90 giorni dopo la randomizzazione |
|
E.5.1.1 | Timepoint(s) of evaluation of this end point |
90 days post-randomisation |
90 giorni dopo la randomizzazione |
|
E.5.2 | Secondary end point(s) |
- Number of days alive without delirium and coma in the ICU - Number of patients with one or more serious adverse reactions to haloperidol and total number of serious adverse reactions to haloperidol - Usage of escape medicine and dosage of escape medicine per patient - Number of days alive without mechanical ventilation in the 90-day period - 1-year mortality post-randomisation - EQ-5D-5L and EQ-VAS one year after randomisation. Patients who have died will be assigned the lowest possible EQ-5D-5L and EQ-VAS score - Cognitive function 1-year after randomisation as assessed using RBANS score at selected sites - Economic analysis |
- numero di giorni in vita senza delirio o coma in ICU - numero di pazienti con 1 o più reazioni avverse e/o numero totale di reazioni avverse all’aloperidolo rispetto al placebo - numero di pazienti che necessitano una o più terapie di “escape” e dosaggio per paziente - numero di giorni in vita senza ventilazione meccanica nei 90 giorni dello studio - mortalità ad 1 anno dopo inclusione - EQ-5D-%l e EQ-VAS un anno dopo la randomizzazione. Ai pazienti deceduti sarà assegnato il punteggio più basso - misurazione delle funzioni cognitive un anno dopo la randomizzazione usando lo score RBANS nei siti selezionati dello studio - Analisi economica |
|
E.5.2.1 | Timepoint(s) of evaluation of this end point |
90 days post-randomisation 1-year post-randomization |
90 giorni dopo la randomizzazione 1 anno dopo la randomizzazione |
|
E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | Yes |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | No |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | Yes |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | Yes |
E.8.1.5 | Parallel group | No |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | Yes |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 2 |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 8 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 30 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
Denmark |
Finland |
France |
Iceland |
Italy |
Netherlands |
Norway |
Spain |
Sweden |
Switzerland |
United Kingdom |
|
E.8.7 | Trial has a data monitoring committee | Yes |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
|
1 year post-randomisation of the last included patient in the trial |
1 anno dopo la randomizzazione dell'ultimo paziente incluso nel trial |
|
E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 3 |
E.8.9.1 | In the Member State concerned months | |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 3 |